Topical Ruxolitinib Cream for Refractory Cutaneous Dermatomyositis

Обзор

This study will assess the safety and efficacy of topical ruxolitinib for treating the refractory cutaneous manifestations in patients with dermatomyositis. The investigators' hypothesis is that topical ruxolitinib will be both safe and effective for such patients.

Подробное описание

Dermatomyositis (DM) is an immune-mediated disease that most commonly affects the skin and the muscles. Cutaneous involvement of DM can lead to ulceration with secondary infection, in addition to permanent skin damage in the form of atrophy, scarring, calcinosis, decreased range of motion or lipoatrophy. Furthermore, persistent cutaneous DM is associated with adverse psychological effects and physical symptoms such as pain, burning, and pruritus. The combination of these contribute to a significant negative impact on DM patients' quality of life. Thus, effective treatment of cutaneous DM represents an important therapeutic goal.

Cutaneous DM symptoms and inflammation are often refractory to currently available topical medications . Additionally, continued topical corticosteroid use is associated with well-known adverse effects, including potential worsening of DM-related skin atrophy and adrenal insufficiency.

Recently, topical ruxolitinib has been developed and studied in several dermatologic conditions. In phase 2 and 3 trials in atopic dermatitis, topical ruxolitinib 1.5% cream resulted in significant efficacy in terms of improving both disease activity and itching, without significant side effects. The investigators propose to study use of topical ruxolitinib 1.5% cream as an adjunct for treatment of refractory cutaneous DM lesions in patients who have previously failed other topical medication options.

Вмешательства

• Препарат Ruxolitinib Topical Cream
  1.5% cream

Первичные конечные точки

• CDASI [Срок оценки: 8 weeks]

Вторичные конечные точки (1)

• CDASI [Срок оценки: week 12]

Критерии участия

Критерии включения

• Patients 18 years and older with refractory cutaneous symptoms related to either classic dermatomyositis (CD), juvenile dermatomyositis (JD), or amyopathic dermatomyositis (AD). Diagnosis will be based on either Bohan and Peter criteria (CD and JD) or Sontheimer's criteria (AD) (19-22).
• Patients must have had a skin biopsy with histologic features consistent with dermatomyositis and current cutaneous manifestations consistent with dermatomyositis.
• Patients will be considered to have refractory disease if cutaneous manifestations exist despite treatment with systemic corticosteroids and at least one steroid-sparing systemic treatment commonly found to be useful in patients with dermatomyositis. These may include azathioprine, cyclosporine, mycophenolate mofetil, IVIG, methotrexate, hydroxychloroquine, cyclophosphamide, chlorambucil, sirolimus, tacrolimus, and rituximab.
• Patients must have sufficiently active cutaneous involvement of dermatomyositis (BSA>1% to <20%, CDASI activity score > 6, and Physician Global Assessment (PGA) activity score >2).
• Patients must have tried and failed at least one commonly prescribed topical medication in the past, with the last application of a topical medication to active skin lesions occurring greater than 2 weeks prior to enrollment.

o Commonly prescribed topical medications for dermatomyositis include corticosteroids or calcineurin inhibitors (tacrolimus or pimecrolimus).

• Patients must have been on a stable systemic medication regimen for at least 2 months (60 days) and must agree to keep the regimen stable throughout the study period. As patients with dermatomyositis are commonly treated with combination regimens that include both topical and systemic immunosuppressive medications, any added risk of adverse effects related to ruxolitinib 1.5% cream is considered negligible.
• Patients must be agreeable to use appropriate contraceptive measures while enrolled in the study.

• Women of childbearing potential must be willing to practice abstinence or use either an oral contraceptive medication or IUD if sexually active.
• Women of childbearing potential must be willing to have monthly urine pregnancy tests while enrolled in the study
• Men of childbearing potential must be willing to practice abstinence or use condoms if sexually active.

Критерии исключения

• Patients with dermatomyositis who have minimal-to-no active cutaneous disease (mild involvement with < 1% total body surface area involved and/or CDASI activity score of < 6).
• Patients who have > 20% total BSA involvement of cutaneous dermatomyositis.
• Patients who have used a common prescription topical medication within the previous 2 weeks.
• Patients whose cutaneous findings are not consistent with dermatomyositis and/or have previous biopsy results suggestive of an alternative diagnosis
• Patients not on stable systemic medication regimens for at least 2 months and/or who will not agree to keep the regimen stable throughout the study period.
• Patients who have previously taken a systemic Janus kinase inhibitor but had a poor response, patients who are currently taking systemic Janus kinase inhibitors, or patients who have used a topical Janus kinase inhibitor for their dermatomyositis or any other condition and had poor responses.
• Patients with inflammatory myositis other than dermatomyositis, such as polymyositis or inclusion body myositis.
• Patients with clear features of an overlap autoimmune myositis or with an inflammatory myositis not consistent with dermatomyositis, such as polymyositis or inclusion body myositis.
• Patients with an active malignancy other than non-melanoma skin cancer, or with malignancy-associated dermatomyositis.
• Patients younger than 18 years old

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Cleveland Clinic — Cleveland

Публикации

• Bailey EE, Fiorentino DF. Amyopathic dermatomyositis: definitions, diagnosis, and management. Curr Rheumatol Rep. 2014 Dec;16(12):465. doi: 10.1007/s11926-014-0465-0. PMID 25366932
• Robinson ES, Feng R, Okawa J, Werth VP. Improvement in the cutaneous disease activity of patients with dermatomyositis is associated with a better quality of life. Br J Dermatol. 2015 Jan;172(1):169-74. doi: 10.1111/bjd.13167. Epub 2014 Nov 30. PMID 24909747
• Huber AM, Kim S, Reed AM, Carrasco R, Feldman BM, Hong SD, Kahn P, Rahimi H, Robinson AB, Vehe RK, Weiss JE, Spencer C; Juvenile Dermatomyositis Research Committee of the Childhood Arthritis and Rheumatology Research Alliance. Childhood Arthritis and Rheumatology Research Alliance Consensus Clinical Treatment Plans for Juvenile Dermatomyositis with Persistent Skin Rash. J Rheumatol. 2017 Jan;44(1) PMID 27803135
• Sanner H, Sjaastad I, Flato B. Disease activity and prognostic factors in juvenile dermatomyositis: a long-term follow-up study applying the Paediatric Rheumatology International Trials Organization criteria for inactive disease and the myositis disease activity assessment tool. Rheumatology (Oxford). 2014 Sep;53(9):1578-85. doi: 10.1093/rheumatology/keu146. Epub 2014 Mar 31. PMID 24692575
• Seshadri R, Feldman BM, Ilowite N, Cawkwell G, Pachman LM. The role of aggressive corticosteroid therapy in patients with juvenile dermatomyositis: a propensity score analysis. Arthritis Rheum. 2008 Jul 15;59(7):989-95. doi: 10.1002/art.23829. PMID 18576304
• Wolstencroft PW, Chung L, Li S, Casciola-Rosen L, Fiorentino DF. Factors Associated With Clinical Remission of Skin Disease in Dermatomyositis. JAMA Dermatol. 2018 Jan 1;154(1):44-51. doi: 10.1001/jamadermatol.2017.3758. PMID 29114741
• Ladislau L, Suarez-Calvet X, Toquet S, Landon-Cardinal O, Amelin D, Depp M, Rodero MP, Hathazi D, Duffy D, Bondet V, Preusse C, Bienvenu B, Rozenberg F, Roos A, Benjamim CF, Gallardo E, Illa I, Mouly V, Stenzel W, Butler-Browne G, Benveniste O, Allenbach Y. JAK inhibitor improves type I interferon induced damage: proof of concept in dermatomyositis. Brain. 2018 Jun 1;141(6):1609-1621. doi: 10.1093 PMID 29741608
• You H, Xu D, Zhao J, Li J, Wang Q, Tian X, Li M, Zeng X. JAK Inhibitors: Prospects in Connective Tissue Diseases. Clin Rev Allergy Immunol. 2020 Dec;59(3):334-351. doi: 10.1007/s12016-020-08786-6. PMID 32222877

Идентификаторы

NCT: NCT06857240 · 23-864

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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